Regulation of pH in the extracellular fluid as well as the intracellular fluid in the immature brain is an important but neglected area. Because bicarbonate can gain rapid access to cerebrospinal fluid (CSF) in neonatal rat, it is of interest to determine how effectively pH is regulated in different regions of the central nervous system (CNS) in infant rats subjected to various acid-base distortions. Since a bicarbonate or hydrogen ion transport system in the choroid plexus has been implicated in the homeostasis of CSF pH in adult animals, it seems desirable to obtain pH data for this secretory epithelium. The use of an indicator method (i.e., the analysis of the steady-state distribution of a weak organic acid, 14C-dimethyloxazolidinedione (DMO), to calculate compartment pH) advantageously permits the stimultaneous determination of pH in several areas of the CNS. Thus, it is possible to study the functional interrelationships (with respect to acid-base metabolism) between choroid plexus, CSF and brain tissue in animals subjected to various stresses. The ontogeny of pH regulatory phenomena in the choroid plexus (and brain) will be studied in the developing rat by analyzing responses to alterations in pCO2 and/or the concentrations of chloride, bicarbonate and hydrogen ion on either or both sides of the blood-CSF and blood-brain barriers. With respect to both the immature chroid plexus and brain, the assessment of 1) the role of the carbonic anhydrase system in regulating CSF bicarbonate concentration, and 2) the buffering capacity of tissue in animals ventilated with CO2, should help to elucidate the nature of acid-base regulation in the incompletely developed CNS. The rat is a convenient model because in this species there is a continual, substantial change throughout the initial month of postnatal life in choroid plexus transport capacity, blood-brain barrier permeability, brain total CO2 content, and the carbonic anhydrase activity in astroglia; thus, the information obtained in this project will delineate the separate influence of these factors on CNS pH homeostasis.